It is well-documented that exposure to ultraviolet radiation (“UVR”) can result in a wide range of adverse health consequences. Excessive exposure to UVB light (290-320 nm) can have both short and longer-term effects. The immediate and primary consequence of unprotected UVB exposure is erythema and sunburn Longer term, childhood sunburns have been correlated with melanoma later in life . UVA light (320-400 nm) penetrates deeper than UVB, reaching both the epidermis and dermis. Repeated exposure to the shorter wavelength UVA II rays (approximately less than about 340 nm) and the longer wavelength UVA I rays (approximately longer than about 340 nm) have been associated with formation of fine lines and wrinkles, irregular skin pigmentation, weakening of the skin's immune system and skin cancer. Other skin disorders associated with overexposure to UVR include non-melanoma skin cancers (i.e., basal cell carcinomas and squamous cell carcinomas), actinic keratoses and premature aging of the skin.
Sunscreen products absorb a certain percentage of light over a specified spectrum, thus preventing potentially harmful erythemal UVR from reaching and damaging the skin. The sun protection factor (“SPF”) listed on sunscreen products is related to this percentage and is intended to communicate the amount of erythemal UVR attenuation. More particularly, numerical SPF theoretically tells the user that he or she is protected X times longer than without sunscreen where X is the labeled SPF. For example, an SPF 33 product would, theoretically, absorb 97% of erythemal UVR and allow 3% of unattenuated light to reach the skin. The user of such an SPF 33 product would conclude that he or she could stay out in the sun 33 times longer than without the sunscreen. However, because most sunscreens are not photostable, labeled SPF is not indicative of the photoprotection actually provided, and thus misleads consumers to believe that they can safely stay out in sun for longer periods of time than that for which the sunscreen actually provides protection. Accordingly, one objective of the present invention is to develop a photostable sunscreen whose labeling accurately communicates to consumers the degree of UVR protection actually provided. Another object of the invention is to provide a sunscreen composition that substantially maintains its SPF rating over an exposure time period of a typical consumer.
One shortcoming of currently available sunscreen products identified by the inventor is that SPF ratings are generated on the basis of sunscreen product exposure to artificial light spectra generated in a solar simulator. While convenient to the chemist testing a formulation, the SPF methodology does not satisfactorily provide an accurate measure of how the formulation will perform under actual conditions of use. Without being bound by theory, the deficiency is believed to be that wavelengths present in natural sunlight that are missing in the artificial spectra, or are present in much lesser relative amounts than in natural sunlight, are responsible (at least in part) for degradation reactions in many sunscreens. These degradation reactions result in lesser amounts of effective sunscreen being present over the exposure time so that effective SPF drops with exposure time. These degradation reactions also generate free radicals, which are associated with adverse health consequences.
The most commonly used simulator is a Xenon Arc solar simulator equipped with a WG320 filter, a UG11 filter, and a dichroic mirror. Such a simulator can produce light spectra meeting the SPF testing specifications set by the European Cosmetic Toiletry and Perfumery Association (“COLIPA”) and routinely used in the US as a spectra standard for SPF testing. The same solar simulator using different filters can produce the Japanese Cosmetic Industry Association (“JCIA”) test spectra and is used for the Persistent Pigment Darkening (“PPD”) in vivo UVA protection test described below. FIG. 1 compares the COLIPA and JCIA spectra with what is generally recognized worldwide as a standard sun spectra (hereinafter “SSS”) and is based on average measurements at noon on June 20th at 40° N latitude.
In contrast to SSS, the COLIPA and JCIA spectra produced in solar simulators eliminate infrared as well as visible light. As seen in FIG. 1, a Xenon Arc solar simulator cuts off radiation at about 380 nm, meaning neither infrared nor visible radiation are emitted. Further, the filters used in solar simulator prevent wavelengths shorter than about 290 nm from being emitted. Sayre et al. have shown that SPF values as tested in the solar simulator are significantly higher than those tested in actual sunlight. For these reasons, the informational value of SPF calculated on the basis of solar simulators is questionable. It should be noted that while the SSS curve of FIG. 1 includes the light spectrum from infrared to visible to ultraviolet, it is an average spectra that varies throughout the year. Among the factors contributing to this variability are proximity and angle of the sun at different latitudes and altitudes at different times of day under variable atmospheric conditions (e.g., cloud cover).
The value of SPF as an accurate measure of protection from UVR has been further called into doubt in the scientific literature. One internationally-recognized authority in the field of photobiology aptly titled a paper “Has SPF had its day?” Several studies have shown that sunburn is as likely to occur in users of high-SPF products than users of no sunscreen at all. Indeed, some researchers have suggested that use of sunscreen products actually increases the risk of developing malignant melanoma. Thus, there exists a long-felt, but as yet unsatisfied need for a sunscreen formulation that accurately communicates photoprotection under actual conditions of use for the entire period of exposure. This need is met by present invention.
Metrics other than SPF are available for indicating degree of photoprotection provided by sunscreens. With respect to UVA protection, two of the most common test methods are the in-vitro Boots Star System and the in-vivo PPD test. The Boots Star System, based on instantaneous readings from a spectrophotometer, indicates the ratio of the average absorbance of UVA energy to UVB energy. A single star is assigned for a UVA/UVB ratio of 0.2-0.4. Two and three stars are assigned to products where the UVA/UVB ratios is 0.4-0.6 and 0.6-0.8, respectively. Four stars are assigned to products with a UVA/UVB ratio of greater than 0.8. PPD measures skin darkening two to four hours after exposure to UVR. A solar simulator emitting a spectra defined by the JCIA is used for the PPD test. However, the degree to which PPD reflects photoprotection under actual conditions of use is limited by the artificial nature of the light source.
Broad-spectrum sunscreens were developed to absorb both UVA and UVB energy. To achieve coverage over the UVA and UVB spectra, multiple sunscreens are selected both on the basis of absorbed wavelength range as well as other properties (i.e., water resistance, hypoallergenicity). A prevailing paradigm in sunscreen formulation has been “more is better”. Many follow the approach that high SPF or more Boots stars can best be achieved by including many sunscreens in high concentrations. Because many sunscreens have decreased performance characteristics (e.g., lower SPF) when exposed to natural light, adherents of this school of formulation add more sunscreen actives than should theoretically be required to achieve a certain SPF. In so doing, they compensate for the degradation that takes place in the laboratory setting. However, this reasoning is flawed. There is markedly more photodegradation in natural sunlight, causing the actual SPF realized by the consumer to be lower.
The “more is better” paradigm also overlooks the fact that among the degradation products in photolabile sunscreens are free radicals which can cause damage to DNA and other cellular molecules. Over time, free radical damage may become irreversible and lead to disease including cancer. Moreover, to the extent that a sunscreen is photolabile under artificial light (e.g., JCIA, COLIPA), that same composition could undergo more photodegradation, and produce more free radicals, when exposed to UVR as well as infrared and visible light under ambient conditions. Thus, a third objective of the present invention is to identify a combination sunscreen composition where after irradiation under ambient light each sunscreen active is photostable and thereby minimize the formation of potentially harmful free radicals.
Avobenzone, which absorbs both UVA I and II is among the more commonly used UVA sunscreens and has been used in combination with other sunscreens in several commercial products. For example, Bullfrog Sunscreen SPF 15 Amphibious Formula was commercially available in the 1980s and contained 2% (wt/wt) avobenzone, 10% (wt/wt) octocrylene, and a third sunscreen, ethyl dihydroxypropyl aminobenzoate. Shade UVAGuard (Schering-Plough HealthCare Products) was sold in the US in 1993 and contained 3% (wt/wt) avobenzone, 3% (wt/wt) oxybenzone, and a third sunscreen, 7.5% (wt/wt) octylmethoxycinnamate. Ombrelle SPF 30 (L'Oréal), sold in Canada, contained 3% avobenzone (wt/wt), 10% octocrylene (wt/wt) and two additional sunscreens, 6% oxybenzone (wt/wt) and 5% octisalate (wt/wt). Avobenzone has not, however, been combined in a sunscreen formulation as claimed in the present invention (i.e., with octocrylene, oxybenzone and no substantial amounts of additional photodegradable sunscreens, preferably substantially no additional sunscreens).
After recognizing the importance of broad spectrum coverage, sunscreen research began to focus on the effectiveness and efficiency of the protection provided. One particularly important parameter that has emerged is photostability. In published articles and meetings of national and international Societies of Cosmetic Chemists, researchers have commented that for maximum safety, broad-spectrum protection must remain efficient throughout the period of exposure to the sun. Many tests for photostability have been proposed. Of these, the majority are performed using artificial light sources (e.g., COLIPA, JCIA). For the reasons discussed above with respect to SPF and UVA protection testing, use of artificial light can strongly confound test results.
Diffey et al. “Sunscreen Product Photostability: A Key Parameter for a More Realistic In Vitro Efficacy Evaluation” Eur. J. Dermatol. 7: 226-228 (1997) proposes a photostability test where thin films of sunscreen product are scanned. UVA and UVB absorbance are plotted before and after irradiation, and the change in the area under the curve represents relative photostability. The Diffey protocol has several limitations. First, the sample area to be scanned by most instruments is very small, making it difficult to ascertain whether the same area was scanned before and after irradiation. If pre- and post-irradiation scans are not taken over precisely the same area, variations in film thickness will skew the results. Moreover, where a composition contains several sunscreens, it is impossible to determine the extent of change for any one sunscreen. This is important because a photolabile sunscreen may undergo significant free radical and/or chemical entity change that could go undetected by the Diffey test.
In U.S. Patent Application Publication Nos. 2004/0047818 and 2004/0047817, Bonda et al. describe a test protocol very similar to Diffey, except that photostability is judged based on absorbance at wavelength(s) of particular interest. This protocol shares the same limitations as Diffey. Further, by limiting the test spectra to artificial light at a specific wavelength, the Bonda proposed method may be even less predictive of photostability than that of Diffey.
Berset et al. “Proposed Protocol for Determination of Photostability Part 1: Cosmetic UV Filters.” Intl. J. Cosmet. Sci., 18(4): 167-177 (1996) teaches a photostability protocol based on comparison of UVR absorption of individual sunscreen actives in solution before and after irradiation. As discussed above, commercially-available, broad spectrum sunscreens contain multiple sunscreen actives as well as other ingredients, the interaction of which may or may not destabilize the composition. Since the Berset method does not account for these interactions, it is not sufficiently predictive of the photostability.
A more accurate approach to quantifying photodegradation, one which would account for production of free radical intermediates, is to analyze the content of individual sunscreen actives in the final commercial product before and after irradiation. Cambon et al. “An In-Vivo Method to Assess the Photostability of UV filters in a Sunscreen” J. Cosmet. Sci., 52: 1-11 (2001) describes a method of measuring photodegradation of sunscreen product that has been directly applied to the skin of human subjects. After irradiation with artificial light (i.e., a solar simulator), residual product is removed via tape strippings, and assayed with HPLC. The use of HPLC produces a true assessment of photodegradation of a sunscreen on exposure to the wavelengths tested. Because the light source used in the Cambon protocol is a solar simulator (i.e., as opposed to natural light), its predictiveness of photostability is limited. Moreover, the ability to control the thickness of application of sunscreen formulation to human skin in a uniform manner is inherently limited, and the absorption of different formulation components in different compositions may vary from subject to subject, with respect to both the sunscreen active and the various excipients, thereby confounding comparisons between tests made on different subjects, at different times, or with different formulations.
As discussed above, avobenzone's broad coverage in the UVA I and UVA II spectra make it a desirable sunscreen. However, avobenzone is widely recognized to be photolabile and to undergo significant photodegradation. For example, as shown in Tables 7 and 8 below, significant percentages of avobenzone were lost when a popular, commercially-available sunscreen product sold in the US and labeled as having an SPF of 30 was exposed to natural sunlight. In a search for photostable broad spectrum sunscreens, researchers have attempted to combine avobenzone with other sunscreens. U.S. Pat. No. 5,576,354 (assigned to L'Oréal) claims a process for stabilizing avobenzone with respect to UV radiation of wavelengths between 280 and 380 nm by adding octocrylene, a UVB absorber, to a sunscreen having 1% to 5% (wt/wt) avobenzone, to result in a concentration of at least 1% octocrylene (wt/wt based on the sunscreen composition). U.S. Pat. No. 5,776,439 discloses a photostable composition comprising from 1% to 10% (wt/wt) avobenzone and from 0.5% to 10% oxybenzone, a UVB absorber.
Published U.S. Patent Application No. 2004/0047818 (Bonda et al.) discloses a sunscreen composition comprising avobenzone, less than 1% octocrylene (wt/wt), and a diester or polyester of naphthalene dicarboxylic acid. The Bonda 2004/0047818 application further teaches the three sunscreens in further combination with oxybenzone. However, none of these putatively stable prior art compositions teach a sunscreen combining avobenzone, octocrylene and oxybenzone alone, with no substantial amount of other photodegradable sunscreen actives or with substantially no other sunscreen active present.
Published U.S. Patent Application No. 2004/0166070 (Galdi et al.) discloses non-pilling UV-photoprotecting alcoholic sunscreen gels comprising acrylates/C12-22 alkylmethacrylate copolymer and an effective amount of at least one UV-A and/or UV-B screening agent where the screening agent comprises avobenzone, octocrylene, oxybenzone and/or octyl salicylate. Lower monohydric alcohols, most commonly ethanol and isopropanol, are used in alcohol sunscreen gel compositions. Example 1 of the Galdi Application discloses an ethanolic sunscreen gel containing acrylates/C12-22 alkylmethacrylate copolymer in combination with four sunscreens (avobenzone, octocrylene, oxybenzone and octyl salicylate). The present invention does not contain one or more elements of the sunscreen composition disclosed in the Galdi Application, including, but not limited to, the following: (i) the present invention may be essentially free of lower monohydric alcohols or free of lower monohydric alcohols; (ii) the present invention may be a sunscreen formulation that is essentially free of, or free of, acrylates/C12-22 alkylmethacrylate copolymer in an effective non-pilling amount used to thicken (i.e., gel) a low molecular weight alcohol (i.e., C1-C4 alcohol); and (iii) compositions of the present invention do not include octyl salicylate (also known as octisalate) which, as discussed below, is not photostable.
Published U.S. Patent Application No. 2005/0013781 (Dueva-Koganov) discloses photoprotective compositions comprising one or more sunscreens and one or more “optimizing agents” which are defined as diols, alcohols, glycols, polyhydric alcohols as well as derivatives or combinations thereof that optimize SPF, Protection Factor A, Boots Star Rating, polarity, critical wavelength or photostability (or any combinations of the foregoing) of the oil phase, water phase, both phases of the composition, or the final sunscreen formulation. Polyhydric alcohols, in particular certain glycols, disclosed in the Dueva-Koganov Application as “optimizing agents” are as follows: pentylene glycol (1,2-pentanediol), neopentyl glycol (neopentanediol), caprylyl glycol (1,2-octanediol), ethoxydiglycol, butylene glycol monopropionate, diethylene glycol monobutyl ether, PEG-7 methyl ether, octacosanyl glycol, arachidyl glycol, benzyl glycol, cetyl glycol (1,2-hexanediol), C14-18 glycol, C15-18 glycol, lauryl glycol (1,2-dodecanediol), butoxydiglycol, 1,10-decanediol, ethyl hexanediol, and combinations thereof.
The Dueva-Koganov Application discloses over thirty sunscreens, including avobenzone, octocrylene and oxybenzone. Table 21 discloses a composition comprising five sunscreens (homosalate, octyl salicylate, oxybenzone, octocrylene and avobenzone) in combination with two optimizing agents (1,2-octanediol and neopentyl glycol). The present invention does not contain one or more elements of the sunscreen composition disclosed in the Dueva-Koganov Application, including, but not limited to, the following: Embodiments of the present invention are substantially free of substantial amounts of optimizing agents, preferably substantially free of optimizing agents, and more preferably free of optimizing agents. In addition, as discussed below, both homosalate and octyl salicylate are not photostable, and compositions containing these sunscreens are not within the scope of the present invention.
U.S. Pat. Nos. 5,576,354 and 5,776,439 and published U.S. Patent Application Nos. 2004/0047817, 2004/0047818, 2004/0166070 and 2005/0013781, are incorporated herein by reference.
The present invention is an improvement of pending U.S. patent application Ser. No. 10/887,464, now Publication No. 2005/0025727. By identifying combination sunscreen product, the present invention meets two long felt but unmet needs: (i) accurately communicating the amount of UVR photoprotection actually provided; and (ii) minimizing the amount of potential harmful free radicals formed as byproducts of photodegradation.